Family Practice Vol. 17, No. 6, 508-513
© Oxford University Press 2000
Hormone replacement therapy: changes in frequency and type of prescription by Dutch GPs during the last decade of the millennium
NIVEL: The Dutch Sentinel Practice Network, The Netherlands.
Correspondence to GA Donker, NIVEL, Postbus 1568, 3500 BN-Utrecht, The Netherlands.
Donker GA, Spreeuwenberg P, Bartelds AIM, van der Velden K and Foets M. Hormone replacement therapy: changes in frequency and type of prescription by Dutch GPs during the last decade of the millennium. Family Practice 2000; 17: 508–513.
Received 19 April 2000; Revised 17 July 2000; Accepted 17 July 2000.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionAcknowledegmentsReferences |
|---|
Objective. The present study was conducted in order to determine the change of frequency and type of hormone replacement therapy (HRT) regimen newly prescribed by Dutch GPs.
Methods. A comparison was made of two data sets (multi-stage random samples) collected in 1987/88 and from 1995 to 1998 concerning women 40 years and older who were newly prescribed HRT.
Results. Compared with 1987/88, 50% more patients were newly prescribed HRT in 1998 (2.0 in 1987/88 and 3.0 in 1998 per 1000 registered women, P < 0.01). The age distribution remained about the same, with a peak between 50 and 54 years in each year of registration. Unopposed oestrogens (including plasters) were prescribed less frequently (1.3
in 1987/88 versus 0.7 in 1998, P < 0.001), and combinations of oestrogen and progestogen more frequently in 1998 (0.2 in 1987/88 versus 1.8 in 1998, P < 0.01). Sequential therapy was prescribed slightly more frequently than continuous therapy (65% sequential therapy in 1995; 55% in 1998). The most frequent reason for starting HRT in 1995–1998 was climacteric symptoms (89–98%), followed by osteoporosis prevention (16–28%) and early menopause (13–25%). Rarely were preventive goals the only reason (6%) for prescribing HRT.
Conclusions. The number of HRT prescriptions increased by 50% over the last decade of the millennium. The age distribution remained the same. There was a tendency to shift from prescribing unopposed oestrogens to combinations of oestrogens and progestogens. Alleviation of climacteric symptoms was the main reason for prescribing HRT throughout the registration period. Prescription of HRT for prevention of osteoporosis and/or cardiovascular disease has so far not been adopted on a large scale by Dutch GPs.
Keywords. General practice, hormone replacement therapy, menopause, osteoporosis, prevention..
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAcknowledegmentsReferences |
|---|
Hormonal treatment of climacteric complaints is effective in many women and may improve their quality of life. However, hormonal replacement therapy (HRT) influences many aspects of health, which are rarely assessed simultaneously, e.g. alleviation of symptoms; prevention of cardiovascular disease and osteoporosis; and risk of breast cancer, endometrial cancer and thromboembolism. Published data are often confusing about outcomes, such as the risk of breast cancer.1–4 Differences exist in the way published clinical studies are perceived by practitioners and patients. In addition, clinical studies are limited to selected groups of women, so doubt about the effects in women not belonging to these groups remains. For instance, although a general consensus exists about the benefit of HRT in preventing osteoporosis, the question of whether HRT is still useful after a certain age remains unanswered.5–7 Patients and physicians are strongly exposed to promotion of HRT for all post-menopausal women due to its ability to prevent osteoporosis and to reduce cardiovascular mortality. Not since the recommendations for treatment of hypertension has a change in medical management had the potential to affect so many people.8 The change in attitude from the caution of the 1970s [when the association between oestrogen (when not combined with progestogen) treatment and endometrial cancer was discovered] to today's positive approach is not without controversy. In the absence of clear guidelines, the decision to prescribe HRT during menopause and to post-menopausal women should be taken after weighing the risks and benefits of treatment in individual women. In practice, the complex decision making is highly influenced by personal concepts of disease and quality of life in patients and their physicians.
Not only is the decision to prescribe HRT or not a complex one, but the choice of drug(s) is also complex. The recent addition of progestogen to oestrogen may prevent endometrial hyperplasia and carcinoma, but may also oppose some of the benefits of oestrogen alone, particularly with respect to the prevention of cardiovascular disease.9,10 In addition, menstrual periods continue with a combined regimen.
In The Netherlands, the GP is the point of first contact for most women in mid-life. The GP plays a key role in further management of menopausal complaints and in initiating HRT. The objective of this study is to describe changes over time in the quantity and type of HRT prescribed by Dutch GPs. The following questions will be answered:
- How does the frequency of HRT prescription by Dutch GPs in women 40 years and older change when comparing 1987/88 and 1995–1998?
- How does the preference of drug regimens for HRT prescribed by Dutch GPs in women 40 years and older change when comparing 1987/88 and 1995–1998?
- What are the reasons for prescribing HRT by Dutch GPs? Does this change in the period 1995–1998?
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAcknowledegmentsReferences |
|---|
Since there was no longitudinal network in general practice of an adequate number of patients over a period of 10 years or more, two data sets representing a random sample of the Dutch general practice population were used: (i) data from the Dutch Sentinel Practice Network; and (ii) data from the Dutch National Survey of Morbidity and Intervention in General Practice.
The Dutch Sentinel Practice Network is a network of 65 GPs (43 sentinel practices) serving a practice population of 146 622 patients in 1998 (1% of the Dutch population). It has been in operation since 1970 to gain insight into morbidity and prescription patterns as recorded by GPs. The population under study is representative of the Dutch population with respect to sex, age, region of The Netherlands and degree of urbanization.11 One of the items recorded since January 1995 to 1998 was the prescription of HRT in women 40 years and older. The GP filled in a questionnaire on every prescription regarding patient's age, complaints, prescribed drug and dose. Physicians also recorded whether the patient had undergone uterus extirpation, and whether the drug prescription was the patient's or doctor's initiative, or both.
The Dutch National Survey of Morbidity and Intervention in General Practice was performed in a random sample of 161 Dutch GPs serving a practice population of ~335 000 patients.12,13 Registration of all contacts of patients with general practice took place in four consecutive periods of 3 months, between 1 April 1987 and 31 March 1988, in order to eliminate seasonal influences. Data were recorded per contact about reasons for encounter, diagnoses, diagnostic procedures, medication prescribed, referrals, other treatment procedures, contact with other care providers and follow-up appointments. Reasons for encounter and diagnoses were recorded with the help of The International Classification of Primary Care (ICPC).14
By comparison of the two above-described data sets in women 40 years and older, a comparison of GPs' prescription of HRT could be made between 1987/88 (National Survey) and 1995–1998 (Sentinel Practice Network). In the Dutch Sentinel Practice Network, women with a first HRT prescription for climacteric complaints, early menopause, osteoporosis (prevention) and prevention of cardiovascular disease were selected. In the National Survey, women with a first HRT prescription for climacteric complaints, osteoporosis and prevention of cardiovascular disease were included. Prescriptions for early menopause, bilateral ovariectomy and osteoporosis prevention could not be included in that data set, as those ICPC codes did not exist in the National Survey in 1987/88. The total number of first prescriptions per 1000 women in each age group and the different regimens of HRT prescribed per 1000 women in each age group were analysed by SPSS.15 The decision to analyse first prescriptions was made in order to exclude bias from differences in duration of data collection beteen the two data sets used. When comparing differences between the National Survey and Sentinel Practices, data were adjusted for differences in duration of data collection by multiplying the number of new prescriptions in the National Survey by four. The Mantel–Haenszel summary chi-square test comparing all registration years was used as a statistical test.16
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAcknowledegmentsReferences |
|---|
Compared with 1987/88, there was an ~50% increase in HRT prescriptions during the years 1995–1998 (2.0
in 1987/88 versus 3.0 in 1998, P < 0.01, Table 1
). The age distribution was quite stable, with a peak between 50 and 54 years throughout the study period (Table 1).
|
Calculated per 1000 registered women in 1995–1998, HRT in women 40 years and older was prescribed more frequently compared with 1987/88 (2.1 in 1987/88 versus 3.0 in 1998, P < 0.01, Table 2
). The preference for type of HRT regimen changed between 1987/88 and 1998. Unopposed oestrogens were prescribed less frequently in 1998 (1.3 in 1987/88 versus 0.7 in 1998, P < 0.001), and combinations of oestrogen and progestogen more frequently (0.2 in 1987/88 versus 1.8 in 1998, P < 0.01, Table 2). Sequential therapy was prescribed more often than continuous therapy, although there was a gradual shift from sequential to continuous therapy in the last few years (from 65% sequential therapy in 1995 to 55% in 1998; not shown). Progestogens and androgens without oestrogens were not prescribed in 1995–1998 (Table 2).
|
The practice of prescribing unopposed oestrogens in women with an intact uterus has almost been abandoned in the last few years (0.7
in 1995 versus 0.1 in 1998, Table 3). However, after uterus extirpation, many women still receive a combination of oestrogen and progestogen, while the intention of preventing carcinoma of the endometrium is not valid in these patients (0.4 in 1995 and in 1998, Table 3). Over the years, a steady number of women (0.3–0.6) are using oral contraceptives probably as a combination for treating climacteric complaints and for oral contraception (Tables 2 and 3
).
|
The most frequent reason for starting HRT in 1995–1998 (as recorded by GPs) is climacteric symptoms (89–98%), followed by osteoporosis prevention (15–28%) and early menopause (13–25%, Table 4
). Physicians were able to give more than one reason for starting HRT in the Sentinel Practices. The type of climacteric symptoms was specified by the GP. Flushes and interrupted sleep due to flushes were mentioned most frequently, but atrophic vulva, irregular vaginal blood loss, loss of libido, depressive feelings and joint aches were also noted. Comparison with 1987/88 is not relevant as early menopause, bilateral ovariectomy and osteoporosis prevention were not included in the list of ICPC codes in 1987/88. In 1995–1998, a minority of HRT prescriptions are for purely preventive reasons (~6%).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAcknowledegmentsReferences |
|---|
The study shows changes in first prescription of HRT between 1987/88 and 1998. In total, the number of HRT prescriptions increased by ~50% between 1987/88 and 1998, but the rate is still low compared with international data. The age distribution remained the same throughout the study period. There was a trend to shift from prescribing unopposed oestrogens towards combinations of oestrogen and progestogen. In The Netherlands, where, in general, prescription of drugs is restrictive and where natural birth methods are still propagated (31% of births take place at the patient's home), the natural course of menopause is also cherished, as shown in the present study.17–19 International data show a much stronger trend. In 1987, HRT was used by an estimated 2.2% of women aged 40–64 years in England, and by 1.0% in Scotland.20 By 1994, this had risen to 21.7% in England and to 20.4% in Scotland, a 10- to 20-fold increase.20
The Nurses Health Study, a large American prospective study, analysed risk of breast cancer in almost 70 000 post-menopausal women. A 30–40% increased risk of developing breast cancer was calculated for women using either oestrogens alone or a combination of oestrogens and progestogens.3,21 The increased risk of developing breast cancer in women using HRT for 5 or more years was even higher (46%) and reached 71% in older women (60–64 years). A meta-analysis of 51 epidemiological studies concerning breast cancer and HRT, which included the Nurses Health Study, confirmed these findings and calculated a 35% increased risk in women using HRT for 5 years or more, and a 
35% risk in women with a low body mass index (BMI).22 Recently, these results were confirmed in another large study of 46 355 post-menopausal women in the USA participating in the Breast Cancer Detection Demonstration Project (BCDDP); a 3 and 12% increased risk per year of use of oestrogen only and oestrogen–progestin combined, respectively, in women with a BMI of 24.4 or less.23 Since the incidence of breast cancer in The Netherlands is already high compared with that of surrounding countries (9500 new cases in 1995), extrapolating the results of these studies to the situation in The Netherlands would mean at least 1000 extra cases of breast cancer per year due to HRT when HRT is prescribed more liberally.24 Besides an increased risk of breast cancer, the increased risk of thromboembolism in users of HRT recently has been stressed again.25 The choice for GPs in prescribing HRT in individual women, taking into account all the advantages and disadvantages, is not an easy task. Patients' request for alleviation of symptoms and the advantages regarding prevention of osteoporosis and cardiovascular disease have to be weighed against increased risks of breast cancer and thromboembolism when prescribing HRT. Patients' age, BMI and family history regarding cancer and thromboembolism may affect this judgement further. More studies are needed to complete the fragmented knowledge of risk and benefits of HRT, but as such studies are still under way, evidence-based medicine should be the basis for prescription of HRT. Dutch GPs have chosen careful prescription of HRT, mainly for alleviation of menopausal symptoms, as shown in the present study. This may well have to do with the attention in Dutch medical journals paid to the increased risk of breast cancer in users of HRT.26–28 In addition, Dutch general practice is geared towards evidence-based medicine. The evidence of previously assumed advantages of HRT (prevention of cardiovascular disease) is contradicted by new research from time to time. A recent randomized trial of oestrogen combined with progestogen failed to show a reduction in the overall rate of coronary heart disease (CHD) events in post-menopausal women with established CHD and again confirmed the increased risk of thromboembolism.29 Evidence from observational studies should be confirmed in clinical trials in order to be adopted into evidence-based medicine practice. The present development of ‘specific oestrogen receptor modulators’ (SERMs) may help to prevent adverse effects of HRT, but they do not alleviate symptoms as well, the main reason for prescribing HRT in The Netherlands. So far, the Dutch College of GPs has not advised their members to prescribe HRT for primary or secondary prevention of osteoporosis due to possible adverse effects in long-term use of HRT and due to losing the benefits within a few years after stopping HRT.30 Despite the low rate of prescribing HRT for primary or secondary prevention of cardiovascular disease, the incidence rate of suspected myocardial infarction in Dutch women 45–64 years of age declined by 32% in 15 years (2.8 per 1000 in 1978 to 1.9 per 1000 in 1991–1994), due mainly to decreased smoking rates and improved serum cholesterol.31
The tendency to shift from prescribing oestrogen towards a combination of oestrogen and progestogens for HRT is supported by the literature on prevention of endometrial carcinoma.26,32–34 Unopposed oestrogen replacement therapy showed an RR of 3.0 for endometrial carcinoma.32 When using oestrogen for 10 years, the RR even increased to 9.5.34 During use, the RR appeared to be 4.1, while no increased risk could be demonstrated when using the combination of oestrogens and progestogens.34
The present study compared two data sets both based on data collection by separate forms. In the National Survey (1987/88) during 3 months per practice, each consultation was duplicated on a separate form by the physicians, while in the Sentinel Practices (1995–1998), selected problems were noted on separate forms for several years. HRT prescription was one of these selected problems. The validity of this study depends on completeness of data collection in both surveys. Confounding factors could occur if the tendency in the Sentinel Practices to forget duplication of the selected problems on separate forms was greater than duplication of all problems on separate forms in the National Survey. Comparison between Sentinel Practices and a computer-based registration network in general practice of 14 physicians (Registration Network Groningen—RNG) in 1995, where the physician's memory is excluded as a possible confounding factor, showed similar prescription rates of HRT in the two data sets. This makes it highly unlikely that the differences found in this study can be attributed to incomplete data collection in the Sentinel Practices. The National Survey shows an incidence of menopausal symptoms of 8.0 per 1000 women per year.35 Comparison with the above-mentioned computer-based registration network in general practice (RNG) shows an incidence of menopausal complaints of 8.9 per 1000 women per year over the years 1993–1996.36 This does not indicate a decrease in incidence of menopausal symptoms presented to the GP. No comparable figure is available in the Sentinel Practices, as these registered only women with menopausal complaints, who also received HRT. Not all women presenting with menopausal symptoms are prescribed HRT. Future longitudinal studies in general practices regarding prescription of HRT would be useful, but in the absence of such longitudinal studies of adequate size and time span, the present study provides useful insights into changes in frequency, type and reason for prescription over time in The Netherlands.
We conclude that promotional activities to prescribe HRT for prevention of osteoporosis and/or cardiovascular disease have so far not been adopted on a large scale by Dutch GPs. The number of HRT prescriptions increased by 50% over 10 years. There is a tendency to shift from prescribing oestrogens to combinations of oestrogens and progestogens. Alleviation of menopausal symptoms was the main reason for prescribing HRT during the last decade of the millennium.
|
Acknowledegments |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAcknowledegmentsReferences |
|---|
We gratefully thank the GPs and their practice assistants, who collected data, and without whom this study would not have been possible.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionAcknowledegmentsReferences |
|---|
1 Rozenberg S, Kroll M, Vandromme J. Decision factors influencing hormone replacement therapy. Br J Obstet Gynaecol 1996; 103: 92–98.
2 Cobleigh MA, Berris RF, Bush T. et al. The Breast Cancer Committees of the Eastern Cooperative Oncology Group. Estrogen replacement therapy in breast cancer survivors. A time for change. J Am Med Assoc 1994; 272: 540–545.[ISI][Medline]
3
Colditz GA, Hankinson SE, Hunter DJ et al. The use of estrogens and progestins and the risk of breast cancer in postmenopausal women. N Engl J Med 1995; 332: 1589–1593.
4 Stanford JL, Weiss NS, Voigt LF, Daling JR, Habel LA, Rossing MA. Combined estrogen and progestin hormone replacement therapy in relation to risk of breast cancer in middle-aged women. J Am Med Assoc 1995; 274: 137–142.[Abstract]
5 Lufkin EG, Wahner HW, O'Fallon WM et al. Treatment of postmenopausal osteoporosis with transdermal estrogen. Ann Intern Med 1992; 117: 1–9.
6
Cauley JA, Seeley DG, Ensrud K, Ettinger B, Black D, Cummings SR. Estrogen replacement therapy and fractures in older women. Study of osteoporotic fractures research group. Ann Intern Med 1995; 122: 9–16.
7
Lindsay R, Tohme JF. Estrogen treatment of patients with established postmenopausal osteoporosis. Obstet Gynecol 1990; 76: 290–295.
8 Delva MD. Hormone replacement therapy. Risks, benefits and costs. Can Fam Physician 1993; 39: 2149–2154.[ISI][Medline]
9
Wood JJ. Hormonal treatment of postmenopausal women. N Engl J Med 1994; 330: 1062–1071.
10 Falkeborn M, Persson I, Adami HO et al. The risk of acute myocardial infarction after oestrogen and oestrogen–progestogen replacement. Br J Obstet Gynaecol 1992; 99: 821–828.[ISI][Medline]
11 NIVEL. Continue morbiditeitsregistratie peilstations Nederland. Utrecht, The Netherlands, 1985.
12 Foets M, Velden J van der, de Bakker D. Dutch National Survey of General Practice. A Summary of the Survey Design. Utrecht: NIVEL, 1992.
13 Bensing JM, Foets M, Velden J van der, Zee J van der. De Nationale Studie van ziekten en verrichtingen in de huisartspraktijk. Huisarts Wet 1991; 34: 51–61.
14 Velden J van der, Schellevis FG, Steen J van der. International Classification of Primary Care. Tabulaire lijst. Utrecht: NIVEL, 1991.
15 Norusis MJ. SPSS/PC+ V2.0 Base Manual. Gorinchem: SPSS International BV, 1990.
16 Rosner B. Fundamentals of Biostatistics. 2nd edn. Boston: PWS Publishers, 1986: 302–368.
17 Foets M, Stokx L. Het voorschrijven van geneesmiddelen in de huisartspraktijk. Medisch Contact 1993; 48: 489–492.
18 Foets M. Essential drugs in the North: a concept in a hostile environment. In Velden J van der, Ginneken JKS van, Velema JP, Walle FB de Wijnen JH van (eds). Health Matters. Public Health in North–South Perspective. Houten/Diegem: Bohn Stafleu Van Loghum, 1995: 332–342.
19 Wiegers T. Home or hospital birth. A prospective study of midwifery care in the Netherlands. [Dissertation]. Utrecht: NIVEL, 1997.
20 Townsend J. Hormone replacement therapy: assessment of present use, costs, and trends. Br J Gen Pract 1998; 48: 955–958.[ISI][Medline]
21
Colditz GA, Willett WC, Speizer FE. Breast cancer and hormone-replacement therapy. N Engl J Med 1995; 333: 1355–1358.
22 Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet 1997; 350: 1047–1059.[ISI][Medline]
23
Schairer C, Lubin J, Troisi R, Sturgeon S, Brinton L, Hoover R. Menopausal estrogen and estrogen–progestin replacement therapy and breast cancer risk. J Am Med Assoc 2000; 283: 485–491.
24 Meijer Van Putten JB. Kankerincidentie gedaald. Ned Tijdschr Geneeskd 1998; 142: 2757.
25
Pérez Gutthann S, Garcia Rodriguez LA, Castellsague J, Oliart AD. Hormone replacement therapy and risk of venous thromboembolism: population based case–control study. Br Med J 1997; 314: 796–800.
26 Burger CW, Koomen I, Peters NAJB, Leeuwen FE van, Kenemans P. Postmenopauzale hormonale suppletietherapie en kanker van de vrouwelijke geslachtshormonen en de mamma. Ned Tijdschr Geneeskd 1997; 141: 368–372.[Medline]
27 Hamerlynck JVThH, Leeuwen FE van. Langdurige postmenopauzale hormoonsubstitutie en borstkankerincidentie: de ‘Nurses’ health study’. Ned Tijdschr Geneeskd 1996; 140: 759–761.[Medline]
28 Rookus MA, Leeuwen FE van, Hamerlynck JVThH. Het laatste woord over hormoonsuppletie en borstkanker. Ned Tijdschr Geneeskd 1998; 142: 111–113.[Medline]
29
Hulley S, Grady D, Bush T et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. J Am Med Assoc 1998; 280: 605–613.
30 Elders P, Van Keimpema JC, Petri H et al. NHG-Standaard Osteoporose. Huisarts Wet 1999; 42: 115–128.
31
Pal-de Bruin KM van der, Verkleij H, Jansen J, Bartelds A, Kromhout D. The incidence of suspected myocardial infarction in Dutch general practice in the period 1978–1994. Eur Heart J 1998; 19: 429–434.
32
Brinton LA, Hoover RN. Estrogen replacement therapy and endometrial cancer risk: unresolved issues. The Endometrial Cancer Collaborative Group. Obstet Gynecol 1993; 81: 265–271.
33 Persson I, Adami HO, Bergkvist L et al. Risk of endometrial cancer after treatment with oestrogens alone or in conjunction with progestogens: results of a prospective study. Br Med J 1989; 298: 147–151.
34 Grady D, Gebretsadik T, Kerlikowske K, Ernster V, Petitti D. Hormone replacement therapy and endometrial cancer risk: a meta analysis. Obstet Gynecol 1995; 85: 304–313.[Abstract]
35 Velden J van der, Bakker D de, Claessens AAMC, Schellevis FG. Morbidity in General Practice. Dutch Survey of General Practice. Utrecht: NIVEL, 1992.
36 Werf G Th van der, Smith RJA, Stewart RE, Meyboom-de Jong B. Spiegel op de huisarts over registratie van ziekte, medicatie en verwijzingen in de geautomatiseerde huisartspraktijk. Universiteitsdrukkerij, Groningen, 1998.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||